Establishment of monoclonal antibodies against cell surface domains of ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth
Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese ha...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2017-01, Vol.482 (4), p.651-657 |
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| creator | Suzuki, Masayo Toki, Hiroe Furuya, Akiko Ando, Hiroshi |
| description | Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008, KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these specifically bound to ASCT2-positive cells, as determined by flow cytometry and immunoprecipitation. In addition, the antibodies suppressed glutamine-dependent growth of WiDr colorectal cancer cells. These results provide evidence supporting the use of MAbs against ASCT2 as an effective therapeutic strategy for cancer treatment.
•Antibodies recognizing alanine-serine-cysteine transporter 2 (ASCT2) were generated.•KM4008, KM4012, and KM4018 antibodies were isolated through a cell-based screen.•Isolated monoclonal antibodies inhibited glutamine-dependent cancer cell growth.•Monoclonal antibodies against ASCT2 can be effective as anti-cancer therapy. |
| doi_str_mv | 10.1016/j.bbrc.2016.11.089 |
| format | Article |
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•Antibodies recognizing alanine-serine-cysteine transporter 2 (ASCT2) were generated.•KM4008, KM4012, and KM4018 antibodies were isolated through a cell-based screen.•Isolated monoclonal antibodies inhibited glutamine-dependent cancer cell growth.•Monoclonal antibodies against ASCT2 can be effective as anti-cancer therapy.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2016.11.089</identifier><identifier>PMID: 27865832</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Transport System ASC - chemistry ; Animals ; Antibodies, Monoclonal - chemistry ; Antineoplastic Agents - chemistry ; ASCT2 ; Cell Proliferation ; CHO Cells ; Cricetinae ; Cricetulus ; Epitopes - chemistry ; Glutaminolysis ; Humans ; Mice ; Minor Histocompatibility Antigens - chemistry ; Monoclonal antibody ; Neoplasms - immunology ; Neoplasms - therapy ; Protein Domains ; Rats ; Rats, Sprague-Dawley ; SLC1A5</subject><ispartof>Biochemical and biophysical research communications, 2017-01, Vol.482 (4), p.651-657</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-6ae1b1d46fa834cada855447f8fb09d3013be8139784694416c3078cf18d04b33</citedby><cites>FETCH-LOGICAL-c356t-6ae1b1d46fa834cada855447f8fb09d3013be8139784694416c3078cf18d04b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2016.11.089$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27865832$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suzuki, Masayo</creatorcontrib><creatorcontrib>Toki, Hiroe</creatorcontrib><creatorcontrib>Furuya, Akiko</creatorcontrib><creatorcontrib>Ando, Hiroshi</creatorcontrib><title>Establishment of monoclonal antibodies against cell surface domains of ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008, KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these specifically bound to ASCT2-positive cells, as determined by flow cytometry and immunoprecipitation. In addition, the antibodies suppressed glutamine-dependent growth of WiDr colorectal cancer cells. These results provide evidence supporting the use of MAbs against ASCT2 as an effective therapeutic strategy for cancer treatment.
•Antibodies recognizing alanine-serine-cysteine transporter 2 (ASCT2) were generated.•KM4008, KM4012, and KM4018 antibodies were isolated through a cell-based screen.•Isolated monoclonal antibodies inhibited glutamine-dependent cancer cell growth.•Monoclonal antibodies against ASCT2 can be effective as anti-cancer therapy.</description><subject>Amino Acid Transport System ASC - chemistry</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antineoplastic Agents - chemistry</subject><subject>ASCT2</subject><subject>Cell Proliferation</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Epitopes - chemistry</subject><subject>Glutaminolysis</subject><subject>Humans</subject><subject>Mice</subject><subject>Minor Histocompatibility Antigens - chemistry</subject><subject>Monoclonal antibody</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - therapy</subject><subject>Protein Domains</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>SLC1A5</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1q3DAUhUVpaCZpX6CLomU3dnRt2SNDN8OQNoWBLJJAd0I_1zMabGkqySl9jL5xbCbtsqsrLt850tEh5COwEhi0N8dS62jKaj6XACUT3RuyAtaxogLG35IVY6wtqg5-XJKrlI6MAfC2e0cuq7VoG1FXK_LnNmWlB5cOI_pMQ0_H4IMZglcDVT47HazDRNVeOZ8yNTgMNE2xVwapDeOyXVSbh-1jdfOw28KmmXWW5gO6SJ0_OO2yC36B9sOU1eg8FhZP6O1yY57GEM-2-xh-5cN7ctGrIeGH13lNnr7ePm7vit39t-_bza4wddPmolUIGixveyVqbpRVomk4X_ei16yzNYNao4C6W4s5M-fQmpqthelBWMZ1XV-Tz2ffUww_J0xZji4t71Aew5QkCF41XDRdO6PVGTUxpBSxl6foRhV_S2ByqUIe5VKFXKqQAHKuYhZ9evWf9Ij2n-Tv38_AlzOAc8pnh1Em49AbtC6iydIG9z__F951m8U</recordid><startdate>20170122</startdate><enddate>20170122</enddate><creator>Suzuki, Masayo</creator><creator>Toki, Hiroe</creator><creator>Furuya, Akiko</creator><creator>Ando, Hiroshi</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170122</creationdate><title>Establishment of monoclonal antibodies against cell surface domains of ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth</title><author>Suzuki, Masayo ; Toki, Hiroe ; Furuya, Akiko ; Ando, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-6ae1b1d46fa834cada855447f8fb09d3013be8139784694416c3078cf18d04b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amino Acid Transport System ASC - chemistry</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antineoplastic Agents - chemistry</topic><topic>ASCT2</topic><topic>Cell Proliferation</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Epitopes - chemistry</topic><topic>Glutaminolysis</topic><topic>Humans</topic><topic>Mice</topic><topic>Minor Histocompatibility Antigens - chemistry</topic><topic>Monoclonal antibody</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - therapy</topic><topic>Protein Domains</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>SLC1A5</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Suzuki, Masayo</creatorcontrib><creatorcontrib>Toki, Hiroe</creatorcontrib><creatorcontrib>Furuya, Akiko</creatorcontrib><creatorcontrib>Ando, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suzuki, Masayo</au><au>Toki, Hiroe</au><au>Furuya, Akiko</au><au>Ando, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Establishment of monoclonal antibodies against cell surface domains of ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2017-01-22</date><risdate>2017</risdate><volume>482</volume><issue>4</issue><spage>651</spage><epage>657</epage><pages>651-657</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008, KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these specifically bound to ASCT2-positive cells, as determined by flow cytometry and immunoprecipitation. In addition, the antibodies suppressed glutamine-dependent growth of WiDr colorectal cancer cells. These results provide evidence supporting the use of MAbs against ASCT2 as an effective therapeutic strategy for cancer treatment.
•Antibodies recognizing alanine-serine-cysteine transporter 2 (ASCT2) were generated.•KM4008, KM4012, and KM4018 antibodies were isolated through a cell-based screen.•Isolated monoclonal antibodies inhibited glutamine-dependent cancer cell growth.•Monoclonal antibodies against ASCT2 can be effective as anti-cancer therapy.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27865832</pmid><doi>10.1016/j.bbrc.2016.11.089</doi><tpages>7</tpages></addata></record> |
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| subjects | Amino Acid Transport System ASC - chemistry Animals Antibodies, Monoclonal - chemistry Antineoplastic Agents - chemistry ASCT2 Cell Proliferation CHO Cells Cricetinae Cricetulus Epitopes - chemistry Glutaminolysis Humans Mice Minor Histocompatibility Antigens - chemistry Monoclonal antibody Neoplasms - immunology Neoplasms - therapy Protein Domains Rats Rats, Sprague-Dawley SLC1A5 |
| title | Establishment of monoclonal antibodies against cell surface domains of ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth |
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